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循环游离微小 RNA 谱反映同卵双胞胎痴呆发展的不一致性。

Circulating, Cell-Free Micro-RNA Profiles Reflect Discordant Development of Dementia in Monozygotic Twins.

机构信息

Department of Public Health, The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, University of Southern Denmark, Odense, Denmark.

Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.

出版信息

J Alzheimers Dis. 2018;63(2):591-601. doi: 10.3233/JAD-171163.

Abstract

We aim to examine if circulating micro-RNA and cytokine levels associate with dementia diagnosis and cognitive scores. To test our hypothesis, we use plasma donated from 48 monozygotic twin pairs in 1997 and 46 micro-RNAs and 10 cytokines were quantified using microfluidic RT-qPCR and multiplex solid-phase immunoassays, respectively. Micro-RNA and cytokine profiling were examined for associations with dementia diagnoses in a longitudinal registry study or with cognitive scores at baseline. Thirty-six micro-RNAs and all cytokines were detected consistently. Micro-RNA profiles associate with diagnoses and cognitive scores at statistically significant levels while cytokine only showed trends pointing at chronic inflammation in twins having or developing dementia. The most notable findings were decreased miR-106a and miR-210, and increased miR-106b expression in twins with a dementia diagnosis. This pioneering evaluation of micro-RNA and cytokine and dementia diagnosis suggests micro-RNA targets in vasculogenesis, lipoprotein transport, and amyloid precursor protein genes.

摘要

我们旨在研究循环 microRNA 和细胞因子水平是否与痴呆症诊断和认知评分相关。为了验证我们的假设,我们使用了 1997 年捐赠的 48 对同卵双胞胎的血浆,并分别使用微流控 RT-qPCR 和多重固相免疫测定法定量了 46 种 microRNA 和 10 种细胞因子。对 microRNA 和细胞因子谱进行了纵向登记研究,以研究其与痴呆症诊断的关联,或与基线时的认知评分相关。检测到了 36 种 microRNA 和所有细胞因子。microRNA 谱与诊断和认知评分显著相关,而细胞因子仅显示出在患有或发展为痴呆症的双胞胎中存在慢性炎症的趋势。最显著的发现是在被诊断为痴呆症的双胞胎中,miR-106a 和 miR-210 的表达降低,miR-106b 的表达增加。这项开创性的 microRNA 和细胞因子与痴呆症诊断的评估表明,microRNA 靶向血管生成、脂蛋白转运和淀粉样前体蛋白基因。

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